TY - JOUR
T1 - Human brain capillary endothelium
T2 - 2-Arachidonoglycerol (endocannabinoid) interacts with endothelin-1
AU - Chen, Ye
AU - McCarron, Richard M.
AU - Ohara, Yukoh
AU - Bembry, Joliet
AU - Azzam, Nabil
AU - Lenz, Fred A.
AU - Shohami, Esther
AU - Mechoulam, Raphael
AU - Spatz, Maria
PY - 2000/8/18
Y1 - 2000/8/18
N2 - In brain, the regulatory mechanism of the endothelial reactivity to nitric oxide and endothelin-1 may involve Ca2+, cytoskeleton, and vasodilator-stimulated phosphoprotein changes mediated by the cGMP/cGMP kinase system. Endothelium of human brain capillaries or microvessels is used to examine the interplay of endothelin-1 with the putative vasorelaxant 2-arachidonoyl glycerol, an endogenous cannabimimetic derivative of arachidonic acid. This study demonstrates that 2-arachidonoyl glycerol counteracts Ca2+ mobilization and cytoskeleton rearrangement induced by endothelin-1. This event is independent of nitric oxide, cyclooxygenase, and lipoxygenase and is mediated in part by cannabimimetic CB1 receptor, G protein, phosphoinositol signal transduction pathway, and Ca2+-activated K+ channels. The induced rearrangements of cellular cytoskeleton (actin or vimentin) are partly prevented by inhibition of protein kinase C or high levels of potassium chloride. The 2-arachidonoyl glycerol-induced phosphorylation of vasodilator-stimulated phosphoprotein is mediated by cAMP. These findings suggest that 2-arachidonoyl glycerol may contribute to the regulation of cerebral capillary and microvascular function.
AB - In brain, the regulatory mechanism of the endothelial reactivity to nitric oxide and endothelin-1 may involve Ca2+, cytoskeleton, and vasodilator-stimulated phosphoprotein changes mediated by the cGMP/cGMP kinase system. Endothelium of human brain capillaries or microvessels is used to examine the interplay of endothelin-1 with the putative vasorelaxant 2-arachidonoyl glycerol, an endogenous cannabimimetic derivative of arachidonic acid. This study demonstrates that 2-arachidonoyl glycerol counteracts Ca2+ mobilization and cytoskeleton rearrangement induced by endothelin-1. This event is independent of nitric oxide, cyclooxygenase, and lipoxygenase and is mediated in part by cannabimimetic CB1 receptor, G protein, phosphoinositol signal transduction pathway, and Ca2+-activated K+ channels. The induced rearrangements of cellular cytoskeleton (actin or vimentin) are partly prevented by inhibition of protein kinase C or high levels of potassium chloride. The 2-arachidonoyl glycerol-induced phosphorylation of vasodilator-stimulated phosphoprotein is mediated by cAMP. These findings suggest that 2-arachidonoyl glycerol may contribute to the regulation of cerebral capillary and microvascular function.
KW - 2-arachidonoglycerol
KW - Brain endothelial function
KW - Cannabinoids
KW - Endothelin-1
KW - Endothelium
UR - http://www.scopus.com/inward/record.url?scp=0034682990&partnerID=8YFLogxK
U2 - 10.1161/01.RES.87.4.323
DO - 10.1161/01.RES.87.4.323
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C2 - 10948067
AN - SCOPUS:0034682990
SN - 0009-7330
VL - 87
SP - 323
EP - 327
JO - Circulation Research
JF - Circulation Research
IS - 4
ER -